This research has two related objectives. The first is to measure the endogenous levels of circulating gonadotropic and gonadal hormones in strains of mice which differ in prenatal mortality as the result of genetic selection, i.e. to determine endocrine pathways contributing to the expression of genetic differences. The second is to utilize this genetic variation as a tool to investigate endocrine mechanisms involved in control of prenatal survival. We have available 9 selection lines developed in this laboratory with average losses per pregnant female ranging from 0.5 to above 3.5 at both pre- and post-implantation stages, and from 1.0 to more than 6.0 in total losses between ovulation and term. Radioimmunoassay of plasma from four of the lines has established that there are significant differences among them in endogenous levels of at least FSH during pregnancy. In one strain, exogenous progesterone treatment is effective in reducing genetically determined post-implantation mortality. In addition to the selection lines, we have two single locus mutants, Ay and p, which have been reported to affect reproduction of females carrying them. We propose to: (1) characterize the selected lines, and strains carrying the two mutant genes, with respect to plasma LH, FSH, prolactin, progesterone and estrogen levels during pregnancy to determine: a) patterns of endocrine variation associated with genetic variation in prenatal loss; b) whether prenatal losses resulting from (1) quantitative genetic differences accumulated by selection and (2) the effects of single major genes, are attributable to similar endocrine deficiencies or imbalances. (2) use exogenous hormone treatments on intact, ovariectomized and hypophysectomized females of appropriate strains to: a) determine if strain variation is due to variation in endogenous hormone levels or in target organ sensitivity, or both; b) test current hypotheses of pregnancy support mechanisms in the species, or modified hypotheses suggested by the results from (1).